Comparison of descending volleys evoked by monophasic and biphasic magnetic stimulation of the motor cortex in conscious humans

The descending spinal volleys evoked by monophasic and biphasic magnetic stimulation of the motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of four conscious human subjects. The results suggest that both phases of the biphasic pulse are capable of activating descending motor output. The pattern of recruitment of descending activity depends on the intensity of the stimulus and the relative threshold of each volley to each direction of current flow.     

The effect on corticospinal volleys of reversing the direction of current induced in the motor cortex by transcranial magnetic stimulation

Descending corticospinal volleys were recorded from a bipolar electrode inserted into the cervical epidural space of four conscious human subjects after monophasic transcranial magnetic stimulation over the motor cortex with a figure-of-eight coil. We examined the effect of reversing the direction of the induced current in the brain from the usual posterior-anterior (PA) direction to an anterior-posterior (AP) direction. The volleys were compared with D waves evoked by anodal electrical stimulation (two subjects) or medio-lateral magnetic stimulation (two subjects). As reported previously, PA stimulation preferentially recruited I1 waves, with later I waves appearing at higher stimulus intensities. AP stimulation tended to recruit later I waves (I3 waves) in one of the subjects, but, in the other three, I1 or D waves were seen. Unexpectedly, the descending volleys evoked by AP stimulation often had slightly different peak latencies and/or longer duration than those seen after PA stimulation. In addition the relationship between the size of the descending volleys and the subsequent EMG response was often different for AP and PA stimulation. These findings suggest that AP stimulation does not simply activate a subset of the sites activated by PA stimulation. Some sites or neurones that are relatively inaccessible to PA stimulation may be the low-threshold targets of AP stimulation.     

Direct demonstration of interhemispheric inhibition of the human motor cortex produced by transcranial magnetic stimulation

 Electromyographic (EMG) responses evoked in hand muscles by a magnetic test stimulus over the motor cortex can be suppressed if a conditioning stimulus is applied to the opposite hemisphere 6–30 ms earlier. In order to define the mechanism and the site of action of this inhibitory phenomenon, we recorded descending volleys produced by the test stimulus through high cervical, epidural electrodes implanted for pain relief in three conscious subjects. These could be compared with simultaneously recorded EMG responses in hand muscles. When the test stimulus was given on its own it evoked three waves of activity (I-waves) in the spinal cord, and a small EMG response in the hand. A prior conditioning stimulus to the other hemisphere suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus when the interstimulus interval was greater than 6 ms. In the spinal recordings, the effect was most marked for the last I-wave (I₃), whereas the second I₂-wave was only slightly inhibited, and the first I-wave (I₁) was not inhibited at all. We conclude that transcranial stimulation over the lateral part of the motor cortex of one hemisphere can suppress the excitability of the contralateral motor cortex. Received: 31 August 1998 / Accepted: 26 October 1998     

Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits

A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below threshold for obtaining electromyographical (EMG) responses in active hand muscles can suppress responses evoked in the same muscles at rest by a suprathreshold magnetic test stimulus given 1–5 ms later. In order to define the mechanism of this inhibitory effect, we recorded descending volleys produced by single and paired magnetic transcranial stimulation of motor cortex through high cervical, epidural electrodes implanted for pain relief in two conscious subjects with no abnormality of the central nervous system. The conditioning stimulus evoked no recognisable descending activity in the spinal cord, whilst the test stimulus evoked 3–4 waves of activity (I-waves). Conditioning stimulation suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus. Inhibition of the descending spinal volleys was most pronounced at ISI 1 ms and had disappeared by ISI 5 ms. It was evident for all components following the I₁-wave, while the I₁-wave itself was not inhibited at all. We conclude that a small conditioning magnetic stimulus can suppress the excitability of human motor cortex, probably by activating local cortico-cortical inhibitory circuits. Received: 24 September 1997 / Accepted: 25 October 1997     

Facilitatory effect on the motor cortex by electrical stimulation over the cerebellum in humans

Electrical stimulation over the cerebellum is known to transiently suppress the contralateral motor cortex in humans. However, projections from the cerebellar nuclei to the primary motor cortex are disynaptic excitatory pathways through the ventral thalamus. In the present investigation we studied facilitatory effects on the motor cortical excitability elicited by electrical stimulation over the cerebellum by recording surface electromyographic (EMG) responses from the first dorsal interosseous (FDI) muscle in nine normal volunteers. For primary motor cortical activation magnetic stimuli were given over the contralateral hand motor area with a figure-of-eight shaped coil with a current to preferentially elicit I3-waves (test stimulus). For cerebellar stimulation high-voltage electric stimuli were given with an anode on the ipsilateral mastoid process and a cathode over the contralateral process as previously described (conditioning stimulus). The effect of conditioning-test interstimulus intervals was investigated. Anodal cerebellar stimuli increased the size of EMG responses to magnetic cortical stimulation at an interstimulus interval of 3 ms. Reversing the current of conditioning stimulus abolished the facilitation. The same (anodal) conditioning stimuli did not affect electrically evoked cortical responses. Based on the effective polarity of the conditioning stimulus and the time course of facilitation we consider that this effect is due to motor cortical facilitation elicited by activation of the excitatory dentatothalamocortical pathway at the deep cerebellar nuclei or superior cerebellar peduncle. We conclude that the motor cortical facilitation is evoked by cerebellar stimulation in humans     

Modulation of motor cortex excitability by median nerve and digit stimulation

We investigated the time course of changes in motor cortex excitability after median nerve and digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APB, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200–600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation. Received: 11 December 1998 / Accepted: 30 April 1999     

Effects of repetitive transcranial magnetic stimulation over dorsolateral prefrontal and posterior parietal cortex on memory-guided saccades

We investigated the role of the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in a visuospatial delayed-response task in humans. Repetitive transcranial magnetic stimulation (20 Hz, 0.5 s) was used to interfere temporarily with cortical activity in the DLPFC and PPC during the delay period. Omnidirectional memory-guided saccades with a 3-s delay were used as a quantifiable motor response to a visuospatial cue. The question addressed was whether repetitive transcranial magnetic stimulation (rTMS) over the DLPFC or PPC during the sensory of memory phase affects accuracy of memory-guided saccades. Stimulation over the primary motor cortex served as control. Stimulation over the DLPFC significantly impaired accuracy of memory-guided saccades in amplitude and direction. Stimulation over the PPC impaired accuracy of memory-guided saccades only when applied within the sensory phase (50 ms after cue offset), but not during the memory phase (500 ms after cue offset). These results provide further evidence for a parieto-frontal network controlling performance of visuospatial delayed-response tasks in humans. It can be concluded that within this network the DLPFC is mainly concerned with the mnemonic respresentation and the PPC with the sensory representation of spatially defined perceptual information. Received: 22 April 1996/Accepted: 16 June 1997     

Short and long duration transcranial direct current stimulation (tDCS) over the human hand motor area

The aim of the present paper is to study effects of short and long duration transcranial direct current stimulation (tDCS) on the human motor cortex. In eight normal volunteers, motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) were recorded from the right first dorsal interosseous muscle, and tDCS was given with electrodes over the left primary motor cortex (M1) and the contralateral orbit. We performed two experiments: one for short duration tDCS (100 ms, 1, 3 or 5 mA) and the other for long duration tDCS (10 min, 1 mA). The stimulus onset asynchrony (SOA) between the onset of tDCS and TMS were 1–7 and 10–120 ms for the former experiment. In the latter experiment, TMS was given 0–20 min after the end of 10 min tDCS. We evaluated the effect of tDCS on the motor cortex by comparing MEPs conditioned by tDCS with control MEPs. Cathodal short duration tDCS significantly reduced the size of responses to motor cortical stimulation at SOAs of 1–7 ms when the intensity was equal to or greater than 3 mA. Anodal short duration tDCS significantly increased MEPs when the intensity was 3 mA, but the enhancement did not occur when using 5 mA conditioning stimulus. Moreover, both anodal and cathodal short duration tDCS decreased responses to TMS significantly at SOAs of 20–50 ms and enhanced them at an SOA of 90 ms. Long duration cathodal tDCS decreased MEPs at 0 and 5 min after the offset of tDCS and anodal long duration tDCS increased them at 1 and 15 min. We conclude that the effect at SOAs less than 10 ms is mainly caused by acute changes in resting membrane potential induced by tDCS. The effect at SOAs of 20–100 ms is considered to be a nonspecific effect of a startle-like response produced by activation of skin sensation at the scalp. The effect provoked by long duration tDCS may be short-term potentiation or depression like effects.     

Comparison of motor effects following subcortical electrical stimulation through electrodes in the globus pallidus internus and cortical transcranial magnetic stimulation

Current concepts of transcranial magnetic stimulation (TMS) over the primary motor cortex are still under debate as to whether inhibitory motor effects are exclusively of cortical origin. To further elucidate a potential subcortical influence on motor effects, we combined TMS and unilateral subcortical electrical stimulation (SES) of the corticospinal tract. SES was performed through implanted depth electrodes in eight patients treated with deep brain stimulation (DBS) for severe dystonia. Chronaxie, conduction velocity (CV) of the stimulated fibres and poststimulus time histograms of single motor unit recordings were calculated to provide evidence of an activation of large diameter myelinated fibres by SES. Excitatory and inhibitory motor effects recorded bilaterally from the first dorsal interosseus muscle were measured after SES and focal TMS of the motor cortex. This allowed us to compare motor effects of subcortical (direct) and cortical (mainly indirect) activation of corticospinal neurons. SES activated a fast conducting monosynaptic pathway to the alpha motoneuron. Motor responses elicited by SES had significantly shorter onset latency and shorter duration of the contralateral silent period compared to TMS induced motor effects. Spinal excitability as assessed by H-reflex was significantly reduced during the silent period after SES. No ipsilateral motor effects could be elicited by SES while TMS was followed by an ipsilateral inhibition. The results suggest that SES activated the corticospinal neurons at the level of the internal capsule. Comparison of SES and TMS induced motor effects reveals that the first part of the TMS induced contralateral silent period should be of spinal origin while its later part is due to cortical inhibitory mechanisms. Furthermore, the present results suggest that the ipsilateral inhibition is predominantly mediated via transcallosal pathways.This paper is dedicated to Bernd-Ulrich Meyer, who died in a plane accident     

中老年人脑白质疏松症的电刺激运动诱发电位研究

目的 :探讨电刺激运动诱发电位在中老年人脑白质疏松的临床应用价值。方法 :用大脑皮层电刺激仪刺激大脑上、下肢皮层运动区及颈椎7、胸椎1 2 棘突的相应皮肤 ,在大鱼际肌及胫前肌记录相应的运动诱发电位 (MEP) ,分别对 30例脑白质疏松的中老年人和 30例无白质疏松的对照组进行测定。结果 :脑白质疏松MEP的异常率 37% ,和正常人比较有显著性差异 (χ2 =9 79,P <0 0 1) ,其异常形式有 :中枢运动传导时间 (CMCT)延长 ,MEP潜伏期 (PL)延长 ,波幅增大和波形消失。下肢CMCT和PL延长与对照组比较有显著差异 (t=11 8,P <0 0 1)。结论 :MEP客观反映了脑白质疏松中老年人的运动传导功能 ,对判断亚临床锥体束损害有实用价值。     

Facilitation of muscle evoked responses after repetitive cortical stimulation in man

The technique of repetitive transcranial magnetic stimulation (rTMS) allows cortical motor areas to be activated by trains of magnetic stimuli at different frequencies and intensities. In this paper, we studied long-term neurophysiological effects of rTMS delivered to the motor cortex at 5 Hz with an intensity of 120% of motor threshold. Each stimulus of the train produced muscle-evoked potentials (MEPs) in hand and forearm muscles, which gradually increased in size from the first to the last shock. After the end of the train, the response to a single-test stimulus remained enhanced for 600–900 ms. In contrast, the train had no effect on the size of the MEPs evoked by transcranial electrical stimulation, while it suppressed H-reflexes in forearm muscles for 900 ms. We conclude that rTMS of these parameters increases the excitability of the motor cortex and that this effect outlasts the train for almost 1 s. At the spinal level, rTMS may increase presynaptic inhibition of Ia afferent fibers responsible for the H-reflex. Received: 12 November 1997 / Accepted: 23 February 1998     

Excitability of the ipsilateral motor cortex during phasic voluntary hand movement

We investigated the influence of self-paced, phasic voluntary hand movement on the excitability of the ipsilateral motor cortex. Single- and paired-pulse transcranial magnetic stimulation (TMS) was applied to the right motor cortex triggered by EMG onset of self-paced movements of individual right hand fingers at intervals ranging from 13 to 2,000 ms. Motor evoked potentials (MEPs) were evaluated in several left arm muscles. Significant suppression of MEP amplitudes was observed when TMS was applied between 35 and 70 ms after EMG onset. This inhibition was diffuse, affecting "adjacent" muscles (those near the homologous muscle in the same extremity) as well as homologous muscles, but more inhibition was observed in adjacent and distal muscles than homologous and proximal muscles. Significant inhibition of ipsilateral motor cortex was produced by index finger movements (both the extensor indicis proprius and the first dorsal interosseus), but not by little finger movement (the abductor digiti minimi). Paired-pulse TMS (at 2- and 10-ms interstimulus intervals) showed a significant increase in intracortical facilitation (ICF) selectively in the homologous muscle when triggered by self-paced movement of the opposite hand, but no change was observed in intracortical inhibition. When stimulation was triggered by self-paced movements, the silent period of the homologous muscle was significantly shortened, but the F-wave and compound muscle action potential were unchanged. Our findings demonstrate that voluntary hand movement exerts an inhibitory influence on a diffuse area of the ipsilateral motor cortex. This inhibitory influence is both time and movement dependent. The inhibitory influence is nonselective, while the facilitatory influence (enhancing ICF) appears to act selectively on the homologous muscles. These effects are most likely mediated by a transcallosal pathway. Electronic Publication     

Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation

 To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9±5.4% vs. 45.6±7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 30–40 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30–40 ms. Threshold elevation was significantly longer than the SP (220±41 vs. 151±28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation. Received: 24 November 1997 / Accepted: 11 August 1998     

Effect of contraction strength on responses in biceps brachii and adductor pollicis to transcranial magnetic stimulation

The sizes of the motor-evoked potentials (MEPs) and the durations of the silent periods after transcranial magnetic stimulation were examined in biceps brachii, brachioradialis and adductor pollicis in human subjects. Stimuli of a wide range of intensities were given during voluntary contractions producing 0–75% of maximal force (maximal voluntary contraction, MVC). In adductor pollicis, MEPs increased in size with stimulus intensity and with weak voluntary contractions (5% MVC), but did not grow larger with stronger contractions. In the elbow flexors, MEPs grew little with stimulus intensity, but increased in size with contractions of up to 50% of maximal. In contrast, the duration of the silent period showed similar changes in the three muscles. In each muscle it increased with stimulus intensity but was unaffected by changes in contraction strength. Comparison of the responses evoked in biceps brachii by focal stimulation over the contralateral motor cortex with those evoked by stimulation with a round magnetic coil over the vertex suggests an excitatory contribution from the ipsilateral cortex during strong voluntary contractions. Received: 12 August 1996 / Accepted: 14 May 1997     

Recruitment of extensor-carpi-radialis motor units by transcranial magnetic stimulation and radial-nerve stimulation in human subjects

The responses of 34 extensor-carpi-radialis motor units to graded transcranial magnetic stimulation (TMS) and electrical stimulation of the radial nerve were investigated in six human subjects. Simultaneously with the recording of the single motor-unit discharges, motor-evoked potentials (MEPs) and H-reflexes evoked by the two types of stimulation were recorded by surface electrodes and expressed as a percentage of the maximal motor response (Mmax). Ten motor units were activated in the H-reflex when it was less than 5% of Mmax, but not in the MEP even when it was 15% of Mmax. The opposite was observed for three motor units. Eleven motor units were recruited by both stimuli, but with significantly different recruitment thresholds. Only ten motor units had a threshold similar to TMS and radial nerve stimulation. From these observations, we suggest that caution should be taken when making conclusions regarding motor cortical excitability based on changes in the size of MEPs, even when it is ensured that there are no similar changes in background EMG-activity or H-reflexes. Received: 20 November 1998 / Accepted: 4 June 1999     

Altered responses of human elbow flexors to peripheral-nerve and cortical stimulation during a sustained maximal voluntary contraction

 The short-latency electromyographic response evoked by transcranial magnetic stimulation (MEP) increases in size during fatigue, but the mechanisms are unclear. Because large changes occur in the muscle action potential, we tested whether changes in the response to stimulation of the peripheral motor nerve could fully account for the increase in the MEP. Subjects (n=8) performed sustained maximal voluntary contractions (MVCs) of the right elbow flexors for 2 min. During the contraction, the MEP and the response to supramaximal stimulation of motor-nerve fibres in the brachial plexus were alternately recorded. During the contraction, responses to motor-nerve stimulation increased in area by 87±35% (mean±SD) in the biceps brachii and 74±30% in the brachioradialis, but the area of the MEPs increased by 153±86% and 175±122%, respectively. Thus, the increase in the MEP was greater than the increase in the peripheral M-wave. The onset latency of the MEP in the biceps brachii increased by 0.7±0.6 ms (range: –0.2 to 1.9 ms) during the sustained contraction. A smaller increase occurred in response to peripheral nerve stimulation (0.3±0.3 ms; from –0.3 to 0.9 ms). In the contralateral elbow flexors, neither responses to transcranial magnetic stimulation nor responses to motor-nerve stimulation changed in size or latency. During the sustained contraction, the short silent period after stimulation of the peripheral nerve (48±5 ms in biceps brachii and 48±4 ms in brachioradialis) increased in duration by about 12 ms (to 61±12 ms and 60±9 ms, respectively), whereas the silent period following transcranial magnetic stimulation increased from 238±39 ms in biceps brachii and 243±34 ms in brachioradialis to 325±41 ms and 343±42 ms, respectively. During a sustained MVC, while the motor responses to peripheral and to cortical stimulation grow concurrently, growth of the MEP cannot be entirely accounted for by changes in the muscle action potential. Hence, some of the increase in MEP size during fatigue must reflect changes in the central nervous system. Increased latency of the MEPs and lengthening of the peripherally evoked silent period are consistent with decreased excitability of the alpha motoneurone pool. Thus, an increased response from the motor cortex to the magnetic stimulus remains a likely contributor to the increase in the size of the MEP in fatigue. Received: 11 September 1998 / Accepted: 28 January 1999     

Primary motor cortex activation by transcranial direct current stimulation in the human brain

Transcranial direct current stimulation (tDCS) can modulate motor cortex excitability in the human brain. We attempted to demonstrate the cortical stimulation effect of tDCS on the primary motor cortex (M1) using functional MRI (fMRI). An fMRI study was performed for 11 right-handed healthy subjects at 1.5 T. Anodal tDCS was applied to the scalp over the central knob of the M1 in the left hemisphere. A constant current with an intensity of 1.0 mA was applied. The total fMRI paradigm consisted of three sessions with a 5-min resting period between each session. Each session consisted of five successive phases (resting-tDCS-tDCS-tDCS-tDCS), and each of the phases was performed for 21s. Our findings revealed that no cortical activation was detected in any of the stimulation phases except the fourth tDCS phase. In the result of group analysis for the fourth tDCS phase, the average map indicated that the central knob of the left primary motor cortex was activated. In addition, there were activations on the left supplementary motor cortex and the right posterior parietal cortex. We demonstrated that tDCS has a direct stimulation effect on the underlying cortex. It seems that tDCS is a useful modality for stimulating a target cortical region.     

Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation

Ten healthy subjects and two patients who had an electrode implanted into the cervical epidural space underwent repetitive transcranial magnetic stimulation (rTMS; 50 stimuli at 5 Hz at active motor threshold intensity) of the hand motor area. We evaluated intracortical inhibition before and after rTMS. In healthy subjects, we also evaluated threshold and amplitude of motor evoked potentials (MEPs), duration of cortical silent period and short-latency intracortical facilitation. rTMS led to a short-lasting reduction in the amount of intracortical inhibition in control subjects with a high interindividual variability. There was no significant effect on other measures of motor cortex excitability. Direct recordings of descending corticospinal volleys from the patients were consistent with the idea that the effect of rTMS on intracortical inhibition occurred at the cortical level. Since the level of intracortical inhibition can be influenced by drugs that act on GABAergic systems, this may mean that low-intensity repetitive magnetic stimulation at 5 Hz can selectively modify the excitability of GABAergic networks in the human motor cortex. Electronic Publication